Hyperthermie in der Onkologie mit einem historischen Überblick

Zusammenfassung

Die Hyperthermie ist eine Behandlungsmethode mit einer langen Tradition. Das Wort Hyperthermie bedeutet erhöhte „Temperatur” und bezeichnet in der Onkologie die Erwärmung von Tumoren. Die Erhöhung der Tumortemperatur hat mehrere günstige physiologische Wirkungen, die eine direkte (Nekrose) oder indirekte (Apoptose) Zerstörung von Tumoren fördern, und das ohne nennenswerte Toxizität. Diese relativ einfache physikalisch-physiologische Methode hat eine wechselhafte Geschichte mit einigen brillanten Erfolgen und vielen großen Enttäuschungen erlebt. Wie lässt sich dies erklären? Welche Möglichkeiten haben wir tatsächlich? Handelt es sich um eine phantastische geniale nichttoxische Behandlungsmethode oder um Quacksalberei einiger Scharlatane?

Summary

Hyperthermia is an ancient treatment. The word hyperthermia means increased temperature referring to the heating of tumors in oncology. An increase of the tumor temperature has several favorable physiological effects promoting direct (necrosis) or indirect (apoptosis) tumor-destructions without mentionable toxicity. This relatively simple, physical-physiological method has a phoenix-like history with some bright successes and many deep disappointments. Why is this an enigma? What do we have in hand? Is it a brilliant miraculous non-toxic treatment or a quackery of some charlatans? We try to answer these questions.

Literatur

• 001 Duin N, Sutcliffe J. A History of Medicine. Simon et Schuster Ltd. London; 1992
• 002 Jones S, Henry W. Hippocrates. Harvard University Press Cambridge, MA, USA; 1959
• 003 Vesalius A. Dehumani corporis fabrica libri septem. 1543
• 004 Warren J C. Surgical observations on Tumors with cases and operations. 1837 (Ref: Pollay M: The first American book on tumors. Thesis, University of Madison, Wisconsin, 1955)
• 005 Seegenschmiedt M H. Vernon C C. A Historical Perspective on Hyperthermia in Oncology. In: Seegenschmiedt MH, Fessenden P, Vernon CC. (eds.) Thermoradiotherapy and thermochemotherapy. Vol. 1. „It was mainly philosophical approach, considering the fire and the heat as a universal priority over the natural „forces”.” Springer Verlag Berlin/Heidelberg; 1995
• 006 Smith E. Egyptian Surgical Papyrus dated around 3000 B.C.  cited by: van der Zee J: Heating the patient: a promising approach?  Ann. Oncol.. 2002;  13 1173-1184
• 007 Medieval literature -. 1. Medieval Turkish Surgical manuscript from Charaf ed-Din, 1465 (Paris, Bibliothèque Nationale), 2. Armamentarium chirurgicum of Johann Schultes, Amsterdam 1672 (Paris, Bibliothèque de Faculté Medicine), cited by: [] Seegenschmiedt MH, Vernon CC: A Historical Perspective on Hyperthermia in Oncology. In: Seegenschmiedt MH, Fessenden P, Vernon CC. (eds.) Thermoradiotherapy and thermochemotherapy. Vol. 1. Springer Verlag Berlin/Heidelberg; 1995
• 008 Busch W. Über den Einfluss welche heftigereErysipeln zuweilig auf organisierte Neubildungen ausüben.  Verh. Naturhist. Preuss Rhein Westphal. 1893;  23 28-30
• 009 Coley W B. The treatment of malignant tumors by repeated inoculations of erysipelas, with a report of ten original cases.  Am. J. Med. Sci.. 1893;  105 488-511
• 010 Westermark F. Über die Behandlung des ulcerierenden Cervixcarcinoms mittels konstanter Wärme.  Zentralbl. Gynaekol.. 1898;  22 1335-1337
• 011 Westermark N. The effect of heat on rat tumors.  Skand. Arch. Physiol.. 1927;  52 257-322
• 012 Overgaard K. Über Wärmetherapie bösartiger Tumoren. Acta Radiol. [Ther.] Stockholm; 1934 15: 89-99
• 013 Muller C. Therapeutische Erfahrungen an 100 mit Kombination von Röntgenstrahlen und Hochfrequenz, resp. Diathermie behandelten bösartigen Neubildungen.  Münchener Medizinische Wochenschrift. 1912;  28 1546-1549
• 014 Dewhirst M W, Prosnitz L, Thrall D, Prescott D, Clegg S, Charles C, MacFall J, Rosner G, Samulski T, Gillette e, LaRue S. Hyperthermic Treatment of Malignant Diseases: Current Status and a View Toward the Future. Seminars in Oncology 1997 24: 616-625
• 015 Urano M, Douple E. (eds.) .Hyperthermia and Oncology:.  Vol. 1. Thermal effects on cells and tissues. VSP BV Utrecht, The Netherlands, 1988; Vol. 2. Biology of thermal potentiation of radiotherapy. VSP BV Utrecht, The Netherlands, 1989, 1992; Vol. 3. Interstitial Hyperthermia: Physics, biology and clinical aspects, VSP BV Utrecht, The Netherlands, 1992; Vol. 4. Chemopotentiation by hyperthermia. VSP BV Utrecht, The Netherlands, 1994
• 016 Seegenschmiedt M H, Fessenden P, Vernon C C. (eds.) .Thermoradiotherapy and thermochemotherapy. Vol. 1: Biology, physiology and physics. Springer Verlag, Berlin/Heidelberg 1995; Vol. 2: Clinical applications. Springer Verlag, Berlin/Heidelberg 1996
• 017 Kosaka M, Sugahara T, Schmidt K L, Simon E. Thermotherapy for Neoplasia, Inflammation, and Pain. Springer Verlag Tokyo; 2001
• 018 International Journal of Hyperthermia.  (The official Journal of the North American Hyperthermia Society, European Society for Hyperthermic Oncology, Asian Society of Hyperthermic Oncology) ISSN 0265-6736  Taylor & Francis.
• 019 Zee J van der, Gonzalez Gonzalez D, Rhoon G C van, Dijk J D van, Putten W L van, Hart A A. Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumors: a prospective, randomised, multicentre trial.  Dutch Deep Hyperthermia Group  The Lancet. 2000;  355 (9210) 1119-1125
• 020 Wust P, Hildebrandt B, Sreenivasa G, Rau B, Gellermann J, Riess H, Felix R, Schlag P M. Hyperthermia in combined treatment of cancer.  The Lancet Oncology. 3 2002;  487-496
• 021 Overgaard J, Gonzalez Gonzalez D, Hulshof M C, Arcangeli G, Dahl O, Mella O, Bentzen S M. Randomised trial of hyperthermia as adjuvant to radiotherapy for rezidivierend or metastatic malignant melanoma.  European Society for Hyperthermic Oncology.  The Lancet. 1995;  345 (8949) 540-543
• 022 Nielsen O S, Horsman M, Overgaard J. A future of hyperthermia in cancer treatment?.  Editorial comment  Eur. J. Canc.. 2001;  37 1587-1589
• 023 Dewey W C, Hopwood L E, Sapareto S A, Gerweck L E. Cellular Response to Combination of Hyperthermia and Radiation.  Radiology. 1977;  123 463-474
• 024 Lindholm C- E. Hyperthermia and Radiotherapy. Ph.D. Thesis. Lund University Malmo, Sweden; 1992
• 025 Hafstrom L, Rudenstam C M, Blomquist E. et al. . Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma of the extremities.  J. Clin. Oncol.. 1991;  9 2091
• 026 Kraybill W, Olenki T. A phase I study of fever-range whole body hyperthermia (FR-WBH) in patients with advanced solid tumors: correlation with mouse models.  Int. J. Hyperthermia. 2002;  18 253-266 and Burd R, Dziedzic ST: Tumor Cell Apoptosis, Lymphocyte Recruitment and Tumor Vascular Changes Are Induced by Low Temperature, Long Duration (Fever-Like) Whole Body Hyperthermia. Journal of Cellular Physiology 1998, 177:137-147 
• 027 Field S B. Biological Aspects of Hyperthermia, Physics and Technology of Hyperthermia. In: Field SB, Franconi C. (eds.) NATO ASI Series, E: Applied Sciences, No.127. Martinus Nijhoff Publ. Dordrecht/Boston; 1987: 19-53
• 028 Szasz A, Szasz O, Szasz N. Electrohyperthermia: a new paradigm in cancer thermapy.  Deutsche Zeitschrift für Onkologie. 2001;  33 91-99
• 029 Katchalsky A, Curran P. Non-equilibrium Thermodynamics in Biophysics. Harvard University Press Cambridge, Massachusetts; 1967
• 030 Hodgkin A L, Huxley A F. A quantitative description of membrane current and its application to conduction and excitation of nerve.  J. Physiol.. 1952;  117 500-544
• 031 de Pomarai D de, Daniels C, David H, Allan J, Duce I, Mutwakil M, Thomas D, Sewell P, Tattersall J, Jones D, Candido P. Non-thermal heat-shock response to microwaves.  Nature. 200?????????????;  405 417-418
• 032 Bukau B, Horwich A L. The HSP70 and HSP60 chaperone machines.  Cell. 1998;  92 351-366
• 033 Head J F, Wang Fen, Lipari C A, Elliot R L. The important role of Infrared Imaging in Breast cancer.  IEEE Engineering in Medicine and Biology. 2000;  19 52-57
• 034 Vaupel P, Kallinowski F P O. Blood flow, oxygen and nutrient supply, and microenvironment of human tumors: a review.  Cancer Res.. 1989;  49 6449-65
• 035 Dudar T E, Jain R K. Differential response of normal and tumor microcirculation to hyperthermia.  Cancer Res.. 1984;  44 605-612
• 036 Song C W, Lokshina A, Rhee J G, Patten M, Lewitt S H. Implication of blood-flow in hyperthermic treatment of tumors.  IEEE Trans. Biomed. Eng. BME. 1984;  31 9-16
• 037 Song C W, Choi I B, Nah B S, Sahu S K, Osborn J L. Microvasculature and Persfusion in Normal Tissues and Tumors. In: Seegenschmiedt MH, Fessenden P, Vernon CC. (eds.) Thermoradiotherapy and thermochemotherapy. Vol. 1. Springer Verlag Berlin/Heidelberg; 1995: 139-156
• 038 Song C W, Park H, Griffin R J. Theoretical and Experimental Basis of Hyperthermia. In: Kosaka M, Sugahara T, Schmidt KL, Simon E. (eds.) Thermotherapy for Neoplasia, Inflammation, and Pain Springer Verlag Tokyo; 2001: 394-407
• 039 Yoshimasa Takana. Thermal Responses of Microcirculation and Modification of Tumor Blood Flow in Treating the Tumors. In: Kosaka M, Sugahara T, Schmidt KL, Simon E. (eds.) Thermotherapy for Neoplasia, Inflammation, and Pain. Springer Verlag Tokyo; 2001: 408-419
• 040 Heilbrunn L V. The colloid chemistry of protoplasm.  Am. J. Physiol. 1924;  69 190-199
• 041 Yatvin M B, Dennis W H. Membrane lipid composition and sensitivity to killing by hyperthermia, Procaine and Radiation. In: Streffer C, van Beuningen D, Dietzel F, Rottingen E, Robinson JE, Scherer E, Seeber S, Trott KR. (eds.) Cancer Therapy by Hyperthermia and Radiation. Urban & Schwarzenberg Baltimore/Munich; 1978: 157-159
• 042 Streffer C. Biological Basis of Thermotherapy (with special reference to Oncology). In: Gautherie M. (ed.) Biological Basis of Oncologic Thermotherapy. Springer Verlag Berlin; 1990: -72
• 043 Bowler K, Duncan C J, Gladwell R T, Davison T F. Cellular heat injury.  Comp. Biochem. Physiol.. 1973;  45A 441-450
• 044 Belehradek J. Physiological aspects of heat and cold.  Am. Rev. Physiol.. 1957;  19 59-82
• 045 Wallach D F H. Action of Hyperthermia and Ionizing radiation on plasma membranes. In: Streffer C, van Beuningen D, Dietzel F, Rottingen E, Robinson JE, Scherer E, Seeber S, Trott KR. (eds.) Cancer Therapy by Hyperthermia and Radiation. Urban & Schwarzenberg Baltimore/Munich; 1978: 19-28
• 046 Nishida T, Akagi K, Tanaka Y. Correlation between cell killing effect and cell-membrane potential after heat treatment: analysis using fluorescent dye and flow cytometry.  Int. J. Hyperthermia. 1997;  13 227-234
• 047 Weiss T F. Cellular Biophysics. Vol. 2. Electrical properties. MIT Press Cambridge, Mass; 1996
• 048 Mikkelsen R B, Verma S P, Wallach D F H. Hyperthermia and the membrane potential of erythrocyte membranes as studied by Raman Spectroscopy. In: Streffer C, van Beuningen D, Dietzel F, Rottingen E, Robinson JE, Scherer E, Seeber S, Trott KR. (eds.) Cancer Therapy by Hyperthermia and Radiation. Urban & Schwarzenberg Baltimore/Munich; 1978: 160-162
• 049 Hahn G M. The heat-shock response: Effects before, during and after Gene activation. In: Gautherie M. (ed.) Biological Basis of Oncologic Thermotherapy. Springer Verlag Berlin; 1990: 135-159
• 050 Hodgkin A L, Katz B. The effect of temperature on the electrical activity of the giant axon of the squid.  J. Physiol.. 1949;  108 37-77
• 051 Weiss T F. Cellular Biophysics. Vol. 1. Transport MIT Press Cambridge, Mass.; 1996
• 052 Dewhirst M W, Ozimek E J, Gross J. et al. . Will hyperthermia conquer the elusive hypoxic cell?.  Radiology. 1980;  137 811-817
• 053 Vaupel  P W, Kelleher D K. Metabolic status and reaction to heat of Normal and tumor tissue. In: Seegenschmiedt MH, Fessenden P, Vernon CC (eds.) Thermoradiotherapy and Thermochemotherapy, Vol. 1. Biology, physiology and physics. Springer Verlag Berlin/Heidelberg; 1996: 157-176
• 054 Keszler G, Csapo Z, Spasokoutskaja T, Sasvary-Szekely M, Virga S, Demeter A, Eriksson S, Staub M. Hyperthermy increase the phosporylation of deoxycytidine in the membrane phospholipid precursors and decrease its incorporation into DNA.  Adv Exper Med Biol.. 2000;  486 33-337
• 055 Dikomey E, Franzke J. Effect of heat on induction and repair of DNA strand breaks in X-irradiated CHO cells.  Int J Radiat Biol. 1992;  61 221-234
• 056 Yutaka Okumura, Makoto Ihara, Tatsuya Shimasaki, Satoshi Takeshita, Kumio Okaichi. Heat Inactivation of DNA-Dependent Protein Kinase: Possible Mechanism of Hyperthermic Radiosensitization. In: Kosaka M, Sugahara T, Schmidt KL, Simon E. (eds.) Thermotherapy for Neoplasia, Inflammation, and Pain. Springer Verlag Tokyo; 2001: 420-423
• 057 Shen R N, Lu L, Young P. et al. . Influence of elevated temperature on natural killer cell activity, lymphokine-activated killer cell activity and lecitin-dependent cytotoxicity of human umbilical cord blood and adult blood cells.  Int J Radiat Oncol Biol Phys. 1994;  29 821-826
• 058 Srivastava P K, DeLeo A B, Old L J. Tumor Rejection Antigens of Chemically Induced Tumors of Inbred Mice.  Proc. Natl. Acad. Sci. USA. 1986;  83 3404-3411
• 059 Csermely P, Schnaider T, Soti C, Prohaszka Z, Nardai G. The 90 kDa Molecular Chaperone Family: Structure, Function and Clinical Applications. A Comprehensive Review.  Pharmacol Therapeutics. 1998;  79 129-168
• 060 Pothmann R. TENS Transkutane elektrische Nervenstimulation in der Schmerztherapie. Hippokrates Verlag Stuttgart; 1996
• 061 Gonzalez-Gonzalez D. Thermo-radiotherapy for tumors of the lower gastro-instenstinal tract. In: Seegenschmiedt MH, Fessenden P, Vernon CC. (eds.) Thermoradiotherapy and Thermochemotherapy, Vol. 1. Biology, physiology and physics. Springer Verlag Berlin/Heidelberg; 1996: 105-119
• 062 Urano M, Douple E. Hyperthermia and Oncology, Vol. 2. Biology of thermal potentiation of radiotherapy. VSP Utrecht, The Netherlands; 1989
• 063 Urano M, Douple E. Hyperthermia and Oncology. Vol. 4. Chemopotentiation by Hyperthermia. VSP Utrecht, The Netherlands; 1994
• 064 Shoji Kawasaki, Jun-Ichi Asaumi, Koichi Shibuya, Masahiro Kuroda, Yoshio Hiraki. Recent Aspects of Elucidating the Cellular Basis of Thermochemotherapy. In: Kosaka M, Sugahara T, Schmidt KL, Simon E. (eds.) Thermotherapy for Neoplasia, Inflammation, and Pain. Springer Verlag Tokyo; 2001: 424-432
• 065 Masunaga S- I, Hiraoka M, Akuta K, Nishimura Y, Nagata Y, Jo S, Takahashi M, Abe M. Non-randomized trials of thermoradiotherapy versus radiotherapy for preoperative treatment of invasive urinary bladder cancer.  J. Jap. Soc. Ther. Radiol. Oncol.. 1990;  2 313-320
• 066 Kodama K, Doi O, Higashiyama M, Yokouchi H, Tatsuda M. Long-term results of postoperative Intrathoracic Chemo-thermotherapy for lung cancer with pleural dissemination.  Cancer. 1993;  72 100-106
• 067 Scott A, Izzo F, Fleming R Y D, Ellis L M, Delrio P, Roh M S, Granchi J, Curley S A. Intraoperative radiofrequency ablation of cryoablation for hepatic malignances.  Amer. J. Surg.. 1999;  178 592-599
• 068 Seegenschmiedt M H, Vernon C C. A Historical Perspective on Hyperthermia in Oncology. In: Seegenschmiedt MH, Fessenden P, Vernon CC. (eds.) Thermoradiotherapy and Thermochemotherapy, Vol. 2: Clinical Applications. Springer Verlag Berlin/Heidelberg; 1995: 3-46
• 069 Perez C A, Kopecky W, Baglan R, Rao D V, Johnson R. Local Microwave Hyperthermia in Cancer Therapy. Preliminary Report.  Henry Ford Hospital Medical Journal. 1981;  29 23-37
• 070 Abe M, Hiraoka M. et al. . Clinical Experience With Microwavce and Radiofrequency Thermotherapy in the Treatment of Advanced Cancer.  Natl Cancer Inst Monogr.. 1982;  61 411-414
• 071 Hiraoka M, Jo S. et al. . Clinical Results of Radiofrequency Hyperthermia Combined With Radiation in the Treatment of Radioresistant Cancers.  Cancer. 1984;  54 2898-2904
• 072 Manning M R, Cetas T C, Miller R C. et al. . Clinical hyperthermia results of a phase I trial employing hyperthermia alone or in combination with external beam or intersitial radiotherapy.  Cancer. 1982;  49 205-216
• 073 Sugarbaker P H, Sugarbaker C, Chang D. Radiofrequency Hyperthermia Alone in the Palliative Treatment of Mucinous Carcinomatosis: Optimizing and Monitoring Heat Delivery. In: Kosaka M, Sugahara T, Schmidt KL, Simon E. (eds.) Thermotherapy for Neoplasia, Inflammation, and Pain. Springer Verlag Tokyo; 2001: 456-462
• 074 Issels R. Hyperthermia combined with chemotherapy - biological rationale, clinical application and treatment results.  Onkologie. 1999;  22 374-381
• 075 Zee J van der. Heating the patient: a promising approach?.  Ann. Oncol.. 2002;  13 1137-1184
• 076 Senior K. Hyperthermia and hypoxia for cancer-cell destruction.  The Lancet Oncol.. 2001;  2 524
• 077 Nielsen O S, Horsman M, Overgaard A. A future for hyperthermia in cancer treatment? (Editorial Comment).  Eur. J. Cancer. 2001;  37 1587-1589
• 078 Watson B W. Reappraisal: The treatment of tumors with direct electric current.  Med. Sci. Res.. 1991;  19 103-105
• 079 Samuelsson L, Jonsson L, Stahl E. Percutaneous treatment of pulmonary tumors by electrolysis.  Radiologie. 1983;  23 284-287
• 080 Miklavcic D, Sersa G, Kryzanowski M. Tumor treatment by direct electric current, tumor temperature and pH, electrode materials and configuration.  Bioelectr. Bioeng.. 1993;  30 209-211
• 081 Katzberg A S. The induction of cellular orientation by low-level electrical currents.  Ann. New York Acad Sci.. 1974;  238 445-450
• 082 Nordenstrom B W E. Biologically Closed Electric Circuits: Clinical experimental and theoretical evidence for an additional circulatory system. Nordic Medical Publications Stockholm, Sweden; 1983
• 083 Nordenstrom B W E. Exploring BCEC-systems (Biologically Closed Electric Circuits). Nordic Medical Publications Stockholm, Sweden; 1998
• 084 Xin Y- L. Organization and Spread electrochemical therapy (ECT) in China.  Eur. J. Surg.. 1994;  S-574 25-30 and Xin Y-L: Advances in the treatment of malignant tumors by electrochemical therapy (ECT). Eur. J. Surg. 1994, S-574:31-36 
• 085 Matsushima Y, Takahashi E, Hagiwara K, Konaka C, Miura H, Kato H, Koshiishi Y. Clinical and experimental studies of anti-tumoral effects of electrochemical therapy (ECT) alone or in combination with chemotherapy.  Eur. J. Surg.. 1994;  S-574 59-67
• 086 Chou C K, Vora N, Li J R, Yen Y, Ren R I, McDougall J A, Zhou B S. Development of Electrochemical treatment at the City of Hope (USA).  In: Bersani (ed.) Electricity and Magnetism in Biology and Medicine.  Kluwer Acad. Press/Plenum Publ.. 1999;  927-930
• 087 Xin Y- L, Xue F- Z, Ge B- S, Zhao F- R, Shi B, Zhang W. Electrochemical Treatment of Lung Cancer.  Bioelectromagnetics. 1997;  18 8-13
• 088 Robertson G S M, Wemys-Holden S A, Dennisson A R, Hall P M, Baxter P, Maddern G J. Experimental study of electrolysis-induced hepatic necrosis.  Brit. J. Surgery. 1998;  85 1212-1216
• 089 Jaroszeski M J, Coppola D, Pottinger C, Benson K, Gilbert R A, Heller R. Treatment of hepatocellular carcinoma in a rat model, using electrochemotherapy.  Eur. J. Cancer. 2001;  37 422-430
• 090 Holandino C, Veiga V F, Rodrigues M L, Morales M M, Capella M A M, Alviano C S. Direct current decreases cell viability but not P-glucoprotein expression and function in human multidrug resistant leukemic cells.  Bioelectromagnetics. 2001;  22 470-478
• 091 Susil R, Semrov D, Miklavcic D. Electric field-induced transmembrane potential depends on cell density and organization.  Electro- and Magnetobiology. 1998;  17 391-399
• 092 The first international conference on the topic was in Beijing, China October 20-22, 1992 (200 Chinese and 30 foreign participants, one-hundred-thirty-six papers were presented), from that time in every second year regularly held, special international organization (IABC) organized with the center in USA.
• 093 Szasz A, Szasz O, Szasz N. Electrohyperthermia: a new paradigm in cancer therapy.  Deutsche Zeitschrift für Onkologie. 2001;  33 91-99
• 094 Holt J A G. Microwaves are not hyperthermia.  The Radiographer. 1988;  35 151-162
• 095 Amichetti M, Romano M, Busana L, Bolner A, Fellin G, Pani G, Tomio L, Valdagni R. Hyperfractionated radiation in combination with local hyperthermia in the treatment of advanced squamous cell carcinoma of the head and neck: a phase I-II study.  Radiother Oncol.. 1997;  45 155-158
• 096 Emami B, Scott C, Perez C A, Asbell S, Swift P, Grigsby P, Montesano A, Rubin P, Curran W, Delrowe J, Arastu H, Fu K, Moros E. Phase III study of interstitial thermoradiotherapy compared with interstitial radiotherapy alone in the treatment of recurrent or persistent human tumors. A prospectively controlled randomized study by the Radiation Therapy Group.  Int J Radiat Oncol Biol Phys.. 1996;  34 (5) 1097-1104
• 097 Datta N R, Bose A K, Kapoor H K, Gupta S. Head and neck cancers: results of thermoradiotherapy versus radiotherapy.  Int J Hyperthermia. 1990;  6 479-486
• 098 Valdagni R, Amichetti M, Pani G. Radical radiation alone versus radical radiation plus microwave hyperthermia for N3 (TNM-UICC) neck nodes: a prospective randomized clinical trial.  Int J Radiat Oncol Biol Phys.. 1988;  15 13-24
• 099 Valdagni R, Amichetti M. Report of long-term follow-up in a randomized trial comparing radiation therapy and radiation therapy plus hyperthermia to metastatic lymphnodes in stage IV head and neck patients.  Int J Radiat Oncol Biol Phys.. 1993;  28 163-169
• 100 Datta N R, Bose A K, Kapoor H K. Thermoradiotherapy in the management of carcinoma cervix (IIIB): a controlled clinical study. Indian Med. Gazette 1987 121: 68-71
• 101 Hornbach N B, Shupe R E, Shidnia H, Marshall C U, Lauer T. Advanced stage IIIB cancer of the cervix treatment by hyperthermia and radiation.  Gynecol. Oncol.. 1986;  23 160-167
• 102 Harima Y, Nagata K, Harima K, Ostapenko V V, Tanaka Y, Sawada S L. A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma.  Int J Hyperthermia. 2001;  17 (2) 97-105
• 103 Rietbroek R C, Schiltuis M S, Bakker P M, Dijk J D P van, Psotma A J, Gonzalez Gonzalez D, Bakker A J, Velden J van der, Helmerhorst T J M, Veenhof C H N. Phase II trial of weekly locoregional hyperthermia and cisplatin in patients with a previously irradiated recurrent carcinoma of the uterine cervix.  Cancer. 1997;  79 935-942
• 104 Harima Y, Nagata K, Harima K, Oka A, Ostapenko V V, Shikata N, Ohnishi T, Tnaka Y. Bax and Bcl-2 protein expression following radiation therapy versus radiation plus thermotherapy in stage IIIB cervical carcinoma.  Cancer. 2000;  88 132-138
• 105 Harima Y, Nagata K, Harima K. et al. . A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIb cervical carcinoma.  Int J Hyperthermia. 2001;  17 97-105
• 106 Kohno I, Kaneshige E, Fujiwara K, Sekiba K. Thermochemotherapy (TC) for gynecologic malignancies. In: Overgaard J (ed): Hyperthermic Oncology. Vol. 1. London; Taylor and Francis 1984: 753-756
• 107 Sherar M, Liu F F, Pintilie M, Levin W, Hunt J, Hill R, Hand J, Vernon C, Rhoon G van, Zee J van der, Gonzalez D G, Dijk J, Whaley J, Machin D. Relationship between thermal dose and outcome in thermoradiotherapy treatments for superficial recurrences of breast cancer: data from a phase III trial.  Int J Radiat Oncol Biol Phys.. 1997;  39 (2) 371-380
• 108 Raymond U, Hiraoka M, Takahashi M, Abe M, Matsuda T, Sugiyama A, Nakada Y, Yamamoto Y, Sugahara T. Thermoradiotherapy of refractory malignant tumors: and experience with microwave and RF capacitive hyperthermia.  Medical Instrumentation. 1984;  18 181-186
• 109 Vernon C C, Hand J W, Field S B. et al. . Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials. International Collaborative Hyperthermia Group.  Int J Radiat Oncol Biol Phys.. 1996;  35 731-744
• 110 Masunaga S, Hiraooka M, Takahashi M, Jo S, Akuta K, Nishimura Y, Nagata Y, Abe M. Clinical results of thermoradiotherapy for locally advanced and/or resurrent breast cancer - comparison of results with radiotherapy alone.  Int. J. Hyperthermia. 1990;  6 487-497
• 111 Feyerabend T, Wiedemann G J, Jager B, Vesely H, Mahlmann B, Richter E. Local hyperthermia, radition and chemotherapy in recurrent breast cancer is feasible and effective except for inflammatory disease.  Int. J. Rad. Oncol.. 2001;  49 1317-1325
• 112 Perez C A, Kuske R R, Emani B, Fineberg B. Irradiation alone or combined with hyperthermia in the treatment of recurrent carcinoma of the breast in the chest wall: A nonrandomized comparison.  Int. J. Hyperthermia. 1986;  2 179-187
• 113 Fuwa N, Morita K, Kimura C, Aoyama K, Muroga M, Yamamoto A. Combined treatment of radio-therapy and local hyperthermia using 8MHz RF-wave for advanced carcinoma of the breast. In: Onoyama Y. (ed.) Hyperthermic Oncology ’86 in Japan. Proceedings of the 33 annual meeting of the Japanese Society of Hyperthermic Oncology. 1986: 337-338
• 114 Engelhard M, Gerhartz H, Brittinger G, Engert A, Fuchs R, Geiseler B, Gerhartz D, Haunauske A R, Hartlapp H J, Huhn D. et al. .Cytokine efficiency in the treatment of high-grade malignant non-Hodgkin's lymphomas: results of a randomized double-blind placebo-controlled study with intensified COP-BLAM +/- rhGM-CSF. Ann Oncol. 1994 5: 123-125
• 115 Shchepotin I B, Evans S R, Chorny V, Osinsky S, Buras R R, Maligonov P, Shabahang M, Nauta R J. Intensive preoperative radiotherapy with local hyperthermia for the treatment of gastric carcinoma.  Surg Oncol.. 1994;  3 (1) 37-44
• 116 Kakehi M, Ueda K, Mukoyima T, Hiraoka M, Seto O, Akanuma A, Nakatsugawa S. Multi-institutional clinical studies on hyperthermia combined with radiotherapy of chemotherapy in advanced cancer of deep-seated organs.  Int. J. Hyperthermia. 1990;  6 619-640
• 117 Nagata Y, Hiraoka m, Nishimura Y, Mausnaga S, Koishi M, Takahashi M, Abe M. Radiofrequency hyperthermia for advanced gastric cancer. In: Gerner EW. (ed.) Hyperthermic Oncology. Tucson, Arizona Board of Regents; 1992: 407-412
• 118 Sugimachi K, Kuwano H, Ide H. et al. . Chemotherapy combined with or without hyperthermia for patients with oesophageal carcinoma: a prospective randomized trial.  Int J Hyperthermia. 1994;  4 485-493
• 119 Kitamura K, Kuwano H, Watanabe M, Nozoe T, Yasuda M, Sumiyoshi K, Saku M, Sugimachi K J. Prospective randomized study of hyperthermia combined with chemoradiotherapy for esophageal carcinoma.  Surg Oncol.. 1995;  60 (1) 55-58
• 120 Sugimachi K, Kitamura K, Baba K. Hyperthermia combined with chemotherapy and irradiation for patients with carcinoma of the oesophagus: a prospective randomized trial.  Int. J. Hyperthermia. 1992;  8 289-295
• 121 Sugimachi K, Kitamura K, Baba K, Ikebe M, Morita M, Matsuda H, Kuwano H. Hyperthermia combined with chemotherapy and irradiation for patients with carcinoma of the oesophagus - A prospective randomized trial.  Int. J. Hyperthermia. 1992;  8 289-295
• 122 Muratkhozhaev N K, Svetitsky P V, Kochegarov A A, Alimnazarov S A, Kuznetsov V N, Shek B A. Hyperthermia in therapy of cancer patients.  Med. Radiol. (Russian). 1987;  32 30-36
• 123 Wang J, Li D, Chen N. Intracavitary microwave hyperthermia combined with external irradiation in the treatment of esophageal cancer.  [Article in Chinese] Zhonghua Zhong Liu Za Zhi. 1996;  18 (1) 51-54
• 124 Kakehi M, Ueda K, Mukojima T. et al. . Multi-institutional clinical studies on hyperthermia combined with radiotherapy or chemotherapy in advanced cancer of deep-seated organs.  Int J Hyperthermia. 1990;  6 719-740
• 125 Kondo M, Oyamada H, Yoshikawa T. Therapeutic effects of chemoembolization using degradable starch micro-spheres and regional hyperthermia on unresectable hepatocellular carcinoma. In: Matsuda T. (ed.) Cancer treatment by hyperthermia and drugs. Taylor & Francis London/Washington DC; 1993: 317-327
• 126 Hiraoka M, Jo S, Dodo Y, Ono K, Takahashi M, Nishida H, Abe M. Clinical results of radiofrequency hyperthermia combined with radiation in the treatment of radioresistant cancers.  Cancer. 1984;  54 2898-2904
• 127 Stewart F A, Denekamp J. The therapeutic advantage of combined heat and X-rays on a mouse fibrosarcoma.  Br. J. Radiol. 1978;  51 307-316
• 128 Colombo R, de Pozzo L F, Gev A. Neoadjuvant combined microwave induced local hyperthermia and topical chemotherapy versus chemotherapy alone for superficial bladder cancer.  J. Urol.. 1996;  155 1227-1232
• 129 Goldobenko G V, Durnov L A, Knysh V I, Amiraslanov A T, Kondratieva A P, Matyakin G G, Tkachev S I, Tseitlin G Y, Ivanov S M, Kozhushkov A I. Experience of the use of thermoradiotherapy of malignant tumors.  Med. Radiol. (Russian). 1987;  32 36-37
• 130 Tsyb A F, Berdov B A. The use of local hyperthermia for therapy of cancer patients.  Med. Radiol. (Russian). 1987;  32 25-29
• 131 Savchenko N E, Zhakov I G, Fradkin S Z, Zhavrid E A. The use of hyperthermia in oncology.  Med. Radiol. (Russian). 1987;  32 19-24
• 132 You Q- S, Wang R- Z, Suen G- Q. Combination preoperative radiation and endocavitary hyperthermia for rectal cancer: long-term results of 44 patients.  Int. J. Hyperthermia. 1993;  9 1924
• 133 Rau B, Wust P, Riess H, Schlag P M. Radiochemotherapy plus hyperthermia in rectal carcinoma. [Article in German].  Schweiz Rundsch Med Prax.. 2001;  90 (14) 587-592
• 134 Rau B, Wust F, Hohenberger P, Loffel J, Huherbein M, Below C, Gellermann J, Speidel A, Vogl T, Ries H, Felix R, Schlag P M. Preoperative hyperthermia combined with radiochemotherapy in locally advanced rectal cancer: A phase II clinical trial.  Ann. Surg.. 1998;  227 380-389
• 135 Abe M, Hiraoka M, Takahashi M, Egawa S, Matda C, Onoyama Y, Morita K, Kakehi M, Sugahara T. Multi-institutional studies on hyperthermia using an 8MHz radiofrequency capacitive heating device (Thermotron RF-8) in combination with radiation for cancer therapy.  Cancer. 1986;  58 1589-1595
• 136 Egawa S, Tsukiyama I, Watanabe s, Ohno Y, Morita K, Tominaga S, Onoyama Y, Hashimoto S, Yanagawa S, Uehgara S, Abe M, Mochizuli S, Sugiyama A, Inoue T. A randomized clinical trial of hyperthermia and radiation versus radiation alonefor superfizially located cancers.  J. Jpn,. Soc. Ther. Radiol. Oncol.. 1989;  1 135-140
• 137 Jo S, Sugahara T, Yamamoto I. Clinical response of hyperthermia using heating equipment thermotron-RF8 in Japan.  Biomed Eng. Appl. Basis Comm.. 1994;  6 340-362
• 138 Lindholm C E, Kjellen E, Nilsson P, Hertzman S. Microwave-induced hyperthermia and radiotherapy in human superficial tumors.  Int. J. Hyperthermia. 1987;  3 393-411
• 139 Uozumi H, Baba Y, Yasunaga T, Ookura M, Takada C, Ueno S, Hoshiko N, Miyao M, Hatanaka Y, Takahashi M. Clinical evaluation of combined hyperthermia and radiation therapy of superfici malignant tumors. In: Onoyama Y. (ed.) Hyperthermic Oncology ’86 in Japan. Proceedings of the 3rd annual meeting of the Japanese Society of Hyperthermic Oncology 1986: 311-312
• 140 Overgaard J, Gonzalez Gonzalez D, Hulshof M C, Arcangeli G, Dahl O, Mella O, Bentzen S M. Hyperthermia as an adjuvant to radiation therapy of recurrent or metastatic malignant melanoma. A multicentre randomized trial by the European Society for Hyperthermic Oncology.  Int J Hyperthermia. 1996;  12 (1) 3-20
• 141 Kim J H, Hahn E W, Ahmed S A. Combination hyperthermia and radiation therapy for malignant melanoma.  Cancer. 1982;  50 478-482
• 142 Engelhardt R, Neumann H, Möller U, Lohr G W. Clinical studies in whole body hyperthermia. In: Sugahara T, Saito M (eds): Hyperthermic Oncology. Vol. 2. London; Taylor and Francis 1989: 509-551
• 143 Karasawa K, Muta N, Nakagawa K, Hasezawa K, Terahara A, Onogi Y, Sakata K- I, Aoki Y, Sasaki Y, Akanuma A. Thermoradiotherapy in the treatment of locally advanced nonsmall cell lung cancer.  Int. J. Radiol. Oncol. Biol. Phys.. 1994;  30 1171-1177
• 144 Imada H, Nomoto S, Tomimatsu A, Kosaka K, Kusano S, Ostapenko V V, Terashima H. Local control of Nonsmall cell lung cancer by radiotherapy combined with high power hyperthermia using an 8MHz RF capacitive device.  Japn. J. Hyperthermic Oncol.. 1999;  15 19-24
• 145 Hiraoka M, Nishimura Y, Nagata Y, Mitsumori M, Okuno Y, Li P I, Takahashi M, Masunaga S, Akuta K, Koishi M, Jo S, Abe M. Clinical results fo thermoradiotherapy for soft tissue tumors.  Int. J. Hyperthermia. 1995;  11 365-377
• 146 Issels R D, Abdel-Rahman S, Salat C, Falk M H, Ochmann O, Wilmanns W. Neoadjuvant chemotherapy combined with regional hyperthermia (RHT) followed by surgery and radiation in primary recurrent high-risk soft tissue sarcomas (HR STS) of adults (updated report).  J. Cancer Res. Clin. Oncol.. 1998;  124 R105
• 147 Eggermont A M, Schraffort-Koops H, Lienart D, Kroon B, vanGeel A N, Hoekstra H J, Lejeune F. Isolated limb perfusion with high dose tumor-necrosis factor-alpha in combination with interferon-gamma and melphalan for non-resectable extremity soft-tissue sarcomas: A multicenter trial.  J. Clin. Oncol.. 1996;  14 2653-2665
• 148 Issels R D, Prenninger S W, Nagele A, Boehm E, Sauer H, Jauch K V, Denecke h, Berger H, Peter K, Wilmanns W. Ifosmamide plus etoposide combined with regional hyperthermia in patients with locally advanced sarcomas: A phase II study.  J. Clin. Oncol.. 1990;  8 1818-1829
• 149 U R, Noell T, Woodward K T, Worde B T, Fishburn R I, Miller L S. Microwave-induced local hyperthermia in combination with radiotherapy of human malignant tumors.  Cancer. 1980;  45 638-646
• 150 Robins H I, Dennis W H, Neville A J. et al. . A non-toxic system for 41.8 C whole-body hyperthermia: results of a phase I study using a radiant heat device.  Cancer Res.. 1985;  45 3937-3944
• 151 Sneed P K, Stauffer P R, McDermott M W, Diederich C J, Lamborn K R, Prados M D, Chang S, Weaver K A, Spry L, Malec M K, Lamb S A, Voss B, Davis R L, Wara W M, Larson D A, Phillips T L, Gutin P H. Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost +/- hyperthermia for glioblastoma multiforme.  Int J Radiat Oncol Biol Phys.. 1998;  40 (2) 287-295
• 152 Szasz A, Vincze G Y, Szasz O, Szasz N. An energy analysis of extracellular hyperthermia, accepted for publication in Magneto- and electrobiology. 2003 in print
• 153 Kotnik T, Miklavcic D. Theoretical evaluation of the distributed power dissipation in biological cells exposed to electric field.  Bioelectromagnetics. 2000;  21 385-394
• 154 Galeotti T, Borrello S, Minotti G, Masotti L. Membrane Alterations in Cancer Cells: the role of Oxy Radicals.  Ann. New York Acad. Sci.. 488 Membrane Pathology, Bianchi G, Carafoli E, Scarpa A, (Eds.), 1986, pp. 468-480 
• 155 Hager E D, Dziambor H, Hohmann D, Gallenbeck D, Stephan M, Popa C. Deep hyperthermia with radiofrequencies in patients with liver metastases from colorectal cancer.  Anticancer Research. 1999;  19 3403-3408
• 156 Hager D, Dziambor H, App E M, Popa C, Popa O, Hertlein M. ASCO 2003 Meeting. Chicago USA; 2003: 470
• 157 Dani A, Varkonyi A, Nyiro I, Osvath M. Clinical experience of elecctro-hyperthermia for advanced pancreatic tumors. ESHO 2003 Conference Munich; 2003: 41

Kontakt: